Arylacetic and Arylpropionic Acids

In a similar scheme, acylation of 2-methoxynaphthalene gives ketone, 15. This is then converted to the acetic acid by the Wilgerodt reaction. Esterification, alkylation of the carbanion (sodium hydride methyl iodide), and finally saponification affords naproxen (17). The intense current effort on nonsteroid antiinflammatory agents and acrylacetic acids in particular make 

It probable that the above are but the forerunners of an extensive series of clinical agents. 

Incorporation of the benzylic carbon of phenylacetic acid into a cyclohexane ring affords an agent whose activity is closely related to that of the narcotic analgesics. This activity is particularly noteworthy for the fact that this structure repre- 

In fact, esters of amino alcohols and 2,2-disubstituted plii iiylacetic acids show useful antitussive activity the mecha-lM iii of action may include bronchiodilation. Double alkylation III the anion of phenylacetonitrile with 1,4-dibromobutane gives llit i cyclopentane-substituted derivative (33). Saponification 

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46).  

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